A novel bilayered mucoadhesive buccal patch of zolmitriptan was prepared using xanthan gum (XG) as mucoadhesive polymer. Hydroxypropyl methylcellulose E-15 was used as film-former and polyvinyl alcohol (PVA) was incorporated, to increase the tensile strength of the patches. To study the effect of independent variables viz. concentrations of XG and PVA, on various dependent variables like in vitro drug release, ex vivo mucoadhesive strength and swelling index, 32 factorial design was employed. In vitro drug release studies of optimized formulation showed initially, rapid drug release; 43.15% within 15 min, followed by sustained release profile over 5 h. Incorporation of 4% dimethyl sulfoxide enhanced drug permeability by 3.29 folds, transported 29.10% of drug after 5 h and showed no buccal mucosal damage after histopathological studies. In conclusion, XG can be used as a potential drug release modifier and mucoadhesive polymer for successful formulation of zolmitriptan buccal patches. {\textcopyright} 2013 Elsevier B.V. All rights reserved.